Improvement in the in vitro development of cloned pig embryos after kdm4a overexpression and an H3K9me3 methyltransferase inhibitor treatment

Weng, Xiaogang; Cai, Mingming; Zhang, Yuting; Yan, Liying; Liu, Cong; Z, Liu

doi:10.1016/j.theriogenology.2019.11.027

Cited by 22 publications

(11 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Meanwhile, we defined TDG as a novel and species-specific regulator to potentiate the developmental competence of SCNT embryos. Recently, the H3K9me3 methyltransferase inhibitor chaetocin exhibited a beneficial effect in pig cloning ( Weng et al., 2020 ). Therefore, combinational use of chaetocin, GSK126, and 5AZA will require optimization to further improve the cloning efficiency.…”

Section: Discussionmentioning

confidence: 99%

TDG is a pig-specific epigenetic regulator with insensitivity to H3K9 and H3K27 demethylation in nuclear transfer embryos

et al. 2021

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

TDG is a pig-specific epigenetic regulator with insensitivity to H3K9 and H3K27 demethylation in nuclear transfer embryos

et al. 2021

View full text Add to dashboard Cite

“…In the previous study, chaetocin was used to downregulate the H3K9me3 level in SCNT embryos to prevent damage following microinjection of Kdm4 mRNA; however, 10 nM chaetocin did not improve the developmental rate of ovine SCNT embryos [ 32 ]. In another study, treatment of porcine SCNT embryos at the four-cell stage, but not the one- or two-cell stage, with 10 nM chaetocin for 6 h significantly increased the rate of development [ 34 ]. In our study, we found an aberrant H3K9me3 level in the pronuclear, two-cell, and four-cell stage of SCNT embryos compared to IVF embryos.…”

Section: Discussionmentioning

confidence: 99%

Chaetocin Improves Pig Cloning Efficiency by Enhancing Epigenetic Reprogramming and Autophagic Activity

Jeong

Sim

Park

et al. 2020

IJMS

View full text Add to dashboard Cite

Efficient epigenetic reprogramming is crucial for the in vitro development of mammalian somatic cell nuclear transfer (SCNT) embryos. The aberrant levels of histone H3 lysine 9 trimethylation (H3K9me3) is an epigenetic barrier. In this study, we evaluated the effects of chaetocin, an H3K9me3-specific methyltransferase inhibitor, on the epigenetic reprogramming and developmental competence of porcine SCNT embryos. The SCNT embryos showed abnormal levels of H3K9me3 at the pronuclear, two-cell, and four-cell stages compared to in vitro fertilized embryos. Moreover, the expression levels of H3K9me3-specific methyltransferases (suv39h1 and suv39h2) and DNA methyltransferases (DNMT1, DNMT3a, and DNMT3b) were higher in SCNT embryos. Treatment with 0.5 nM chaetocin for 24 h after activation significantly increased the developmental competence of SCNT embryos in terms of the cleavage rate, blastocyst formation rate, hatching rate, cell number, expression of pluripotency-related genes, and cell survival rate. In particular, chaetocin enhanced epigenetic reprogramming by reducing the H3K9me3 and 5-methylcytosine levels and restoring the abnormal expression of H3K9me3-specific methyltransferases and DNA methyltransferases. Chaetocin induced autophagic activity, leading to a significant reduction in maternal mRNA levels in embryos at the pronuclear and two-cell stages. These findings revealed that chaetocin enhanced the developmental competence of porcine SCNT embryos by regulating epigenetic reprogramming and autophagic activity and so could be used to enhance the production of transgenic pigs for biomedical research.

show abstract

“…H3K9me3 constitutes a major epigenetic barrier in mammalian SCNT embryos; microinjection of mRNA encoding the H3K9me3-specific demethylase of the KDM family significantly improved epigenetic reprogramming efficiency and SCNT embryo development (Matoba et al, 2014;Chung et al, 2015;Liu et al, 2018). Recently, chaetocin was reported to significantly increase epigenetic reprogramming and SCNT embryo development by reducing H3K9me3 levels in pigs (Jeong et al, 2020;Weng et al, 2020). Histone acetylation is also an important feature of epigenetic reprogramming.…”

Section: Discussionmentioning

confidence: 99%

Combined Chaetocin/Trichostatin A Treatment Improves the Epigenetic Modification and Developmental Competence of Porcine Somatic Cell Nuclear Transfer Embryos

Jeong

Yang

Park

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Developmental defects in somatic cell nuclear transfer (SCNT) embryos are principally attributable to incomplete epigenetic reprogramming. Small-molecule inhibitors such as histone methyltransferase inhibitors (HMTi) and histone deacetylase inhibitors (HDACi) have been used to improve reprogramming efficiency of SCNT embryos. However, their possible synergistic effect on epigenetic reprogramming has not been studied. In this study, we explored whether combined treatment with an HMTi (chaetocin) and an HDACi (trichostatin A; TSA) synergistically enhanced epigenetic reprogramming and the developmental competence of porcine SCNT embryos. Chaetocin, TSA, and the combination significantly increased the cleavage and blastocyst formation rate, hatching/hatched blastocyst rate, and cell numbers and survival rate compared to control embryos. In particular, the combined treatment improved the rate of development to blastocysts more so than chaetocin or TSA alone. TSA and combined chaetocin/TSA significantly reduced the H3K9me3 levels and increased the H3K9ac levels in SCNT embryos, although chaetocin alone significantly reduced only the H3K9me3 levels. Moreover, these inhibitors also decreased global DNA methylation in SCNT embryos. In addition, the expression of zygotic genome activation- and imprinting-related genes was increased by chaetocin or TSA, and more so by the combination, to levels similar to those of in vitro-fertilized embryos. These results suggest that combined chaetocin/TSA have synergistic effects on improving the developmental competences by regulating epigenetic reprogramming and correcting developmental potential-related gene expression in porcine SCNT embryos. Therefore, these strategies may contribute to the generation of transgenic pigs for biomedical research.

show abstract

Improvement in the in vitro development of cloned pig embryos after kdm4a overexpression and an H3K9me3 methyltransferase inhibitor treatment

Cited by 22 publications

References 24 publications

TDG is a pig-specific epigenetic regulator with insensitivity to H3K9 and H3K27 demethylation in nuclear transfer embryos

TDG is a pig-specific epigenetic regulator with insensitivity to H3K9 and H3K27 demethylation in nuclear transfer embryos

Chaetocin Improves Pig Cloning Efficiency by Enhancing Epigenetic Reprogramming and Autophagic Activity

Combined Chaetocin/Trichostatin A Treatment Improves the Epigenetic Modification and Developmental Competence of Porcine Somatic Cell Nuclear Transfer Embryos

Contact Info

Product

Resources

About